The NSBCC is organized to take advantage of the state-of-the-art in the science &engineering of nanotechnology (Caltech), the state-of-the-art in the systems biology, and the state-of-the-art in cancer biology and clinical oncology (The UCLA Geffen School of Medicine, the Jonsson Comprehensive Cancer Center &the translational sciences Institute for Molecular Medicine. The NSBCC vision is to utilize the measurement and analysis needs of systems approaches to cancer biology and clinical oncology to drive the science and engineering of new technologies, and to then move those technologies, computational tools and science into an expanded clinical research and clinical care settings through our partnerships with JCCC and IMED. Further development and impact is through commercialization of technologies with for-profit partners. Those technologies can, in addition, open up new scientific and clinical opportunities through enabling access to biological information and solutions to problems that were previously not possible. Over the past 4 years we have built a community of cancer biologists, clinical oncologists, systems biologists, physical scientists and engineers who have worked together to demonstrate extremely rapid pathways from concept to clinic for in vivo molecular imaging diagnostics, in vitro diagnostics, and nanotherapeutics. The new IMED translation medicine facility further expands our avenue from basic science to patient care. The proposed NSBCC will build upon current momentum and will focus on projects that are at the heart of some of the most challenging problems in cancer biology and clinical oncology today. The major targeted cancers are glioblastoma and melanoma, with applications to ovarian cancer during the latter stages of the funding cycle. Central themes are early detection of cancer and enabling technologies for targeted therapies. For all projects, pathways from benchtop to bedside are elaborated. Partnerships with JCCC and IMED, several biotechnology companies, and a number of other NCI-funded and foundation funded programs (for supporting relevant clinical trials and human studies) leverage the NSBCC resources. Public Health Relevance: Technologies and biological information developed by this CCNE provides a pathway for the early detection and informative diagnosis of melanoma, glioblastoma, and ovarian cancers through in vitro diagnostics and in vivo molecular imaging. Direct applications to targeted therapies, including molecularly targeted therapies adoptive T cell immunotherapies, and siRNA therapies, are explored within the proposed Projects.